In our laboratory we have determined that from 2/3 to 4/5 of schizophrenic patients and a large number of their first-degree relatives have defective smooth pursuit eye movements. In contrast, few nonschizophrenic patients and their relatives show this dysfunction. This discovery suggests (1) that core attentional and neuromuscular processes are involved; and (2) that the dysfunction may be a genetic marker for vulnerability to schizophrenic illness. The proposed project will investigate these two implications for our work. (A) We will conduct a genetic mapping of the eye-tracking dysfunction within first-degree families of schizophrenic patients. (B) We will investigate in an animal model the effects on eye tracking not only of specific compounds like long-term doses of phenothiazines, but also of various cholinergic and anticholinergic drugs. The purpose of this line of investigation is to see if drugs which alter the functioning of these systems influence smooth pursuit eye movements. (C) We will follow up over several years patients who have been tested by us in order to correlate clinical course with any vicissitudes in eye-tracking patterns. BIBLIOGRAPHIC REFERENCES: Holzman, P.S. The influence of theoretical models on the treatment of the schizophrenias. In M.M. Gill and P.S. Holzman (Eds.), Psychology Versus Metapsychology: Psychoanalytic Essays in Memory of George S. Klein. Psychological Issues, 1976, Vol. 9, Mono. 36. Otteson, J. & Holzman, P.S. Cognitive controls and psychopathology. Journal of Abnormal Psychology, 1976, 85, 125-189.